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. 2018 Dec;16(4):571-579.
doi: 10.1111/vco.12424. Epub 2018 Aug 8.

In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers

Sita S Withers  1 , Daniel York  1 , Eric Johnson  2 , Sami Al-Nadaf  3 , Katherine A Skorupski  2 , Carlos O Rodriguez Jr  4 , Jenna H Burton  2 , Teri Guerrero  3 , Kriste Sein  3 , Luke Wittenburg  1 , Robert B Rebhun  1
Affiliations

In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers

Sita S Withers et al. Vet Comp Oncol. 2018 Dec.

Abstract

Curcumin has well-established anti-cancer properties in vitro, however, its therapeutic potential has been hindered by its poor bioavailability. Lipocurc is a proprietary liposome-encapsulated curcumin formulation that enables intravenous delivery and has been shown to reach its highest concentration within lung tissue. The goal of this study was to characterize the anti-cancer and anti-angiogenic activity of Lipocurc in vitro, in addition to evaluating Lipocurc infusions in dogs with naturally occurring cancer. We therefore evaluated the effect of Lipocurc, relative to free curcumin, on the viability of canine osteosarcoma, melanoma and mammary carcinoma cell lines, as well as the ability of Lipocurc to inhibit endothelial cell viability, migration and tube formation. We also undertook a pilot clinical trial consisting of four weekly 8-hour Lipocurc infusions in 10 cancer-bearing dogs. Tumour cell proliferation was inhibited by curcumin at concentrations exceeding those achievable in the lung tissue of dogs. Similarly, equivalent high concentrations of Lipocurc and curcumin also inhibited endothelial cell viability, migration and tube formation. Four out of six dogs completing planned infusions of Lipocurc experienced stable disease; however, no radiographic responses were detected.

Keywords: curcumin; dogs; liposomes; lung; metastasis.

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Conflict of interest statement

Conflict of Interest:

The authors have no conflicts of interest in regards to the work published in this manuscript.

Figures

Figure 1
Figure 1
Concentration dependent effects of curcumin and Lipocurc on cancer cell viability. cOSA (Abrams, D17), hOSA (MG63, U2OS), canine mammary carcinoma (CMT12, CMT27), and canine melanoma (UCDK9M3, UCDK9M5) cell lines were exposed to increasing concentrations of curcumin (black) or Lipocurc (grey). Viability was assessed via an MTS assay after 72 hours of drug exposure. Values represent the proportion of viable cells remaining compared to untreated controls. Error bars represent standard deviation. Results are representative of 2 separate experiments.
Figure 2
Figure 2
Figure 2A – Concentration dependent effects of curcumin and Lipocurc on LungEC proliferation assessed with an MTS assay after 72 hours of drug exposure. Values represent the proportion of viable cells remaining compared to untreated controls. Error bars represent standard deviation. Results are representative of 2 separate experiments. Figure 2B – Curcumin and Lipocurc inhibit LungEC migration at a concentration of 4000 ng/ml after 5 and 9 hours. Error bars represent the standard deviation. Results are representative of 2 separate experiments. **= P≤0.01; ***= P≤0.001; ****= P≤0.0001 Figure 2C – Concentration dependent effects of curcumin and Lipocurc on LungEC tube formation. Results are representative of 2 separate experiments.
Figure 2
Figure 2
Figure 2A – Concentration dependent effects of curcumin and Lipocurc on LungEC proliferation assessed with an MTS assay after 72 hours of drug exposure. Values represent the proportion of viable cells remaining compared to untreated controls. Error bars represent standard deviation. Results are representative of 2 separate experiments. Figure 2B – Curcumin and Lipocurc inhibit LungEC migration at a concentration of 4000 ng/ml after 5 and 9 hours. Error bars represent the standard deviation. Results are representative of 2 separate experiments. **= P≤0.01; ***= P≤0.001; ****= P≤0.0001 Figure 2C – Concentration dependent effects of curcumin and Lipocurc on LungEC tube formation. Results are representative of 2 separate experiments.
Figure 2
Figure 2
Figure 2A – Concentration dependent effects of curcumin and Lipocurc on LungEC proliferation assessed with an MTS assay after 72 hours of drug exposure. Values represent the proportion of viable cells remaining compared to untreated controls. Error bars represent standard deviation. Results are representative of 2 separate experiments. Figure 2B – Curcumin and Lipocurc inhibit LungEC migration at a concentration of 4000 ng/ml after 5 and 9 hours. Error bars represent the standard deviation. Results are representative of 2 separate experiments. **= P≤0.01; ***= P≤0.001; ****= P≤0.0001 Figure 2C – Concentration dependent effects of curcumin and Lipocurc on LungEC tube formation. Results are representative of 2 separate experiments.
Figure 3
Figure 3
HCT of the 6 dogs with anemia or decreased HCT throughout treatment.
See this image and copyright information in PMC

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